Microspheres composed of inert or comestible materials are used in various industries. In the pharmaceutical industry, for instance, such microspheres typically are used for applications such as solid dosage delivery systems with coatings for controlled release formulas. The microspheres, also called “nonpareils,” can be used as the seed for drug layering and optional subsequent application of various coatings. The coated microspheres can then be incorporated into tablets, capsules, powders, suspensions or other dosage forms.
The use of microspheres in controlled release solid dosage forms is believed to allow the tablet, capsule or powder to release the active ingredient over time at a controlled rate. This dosage form in many embodiments is believed not only to insure an accurate dose, but also to distribute the dose throughout the gastrointestinal tract instead of in one location. This is understood to decrease an undesirable pharmacological effect known as “dose dumping” and related toxic effects from the active ingredient.
Commercially available microspheres include sugar-based microspheres, microcrystalline cellulose-based microspheres and some starch-based microspheres. Sugar microspheres typically include 90 to 95 percent sucrose and 5 to 10 percent starch as the binder. These microspheres are relatively cost effective, and are satisfactory in many applications. It can be difficult to prepare sugar microspheres having a particle size under 400 microns, however. Also, conventional techniques for preparing sugar-based microspheres can provide particle size distribution of the microspheres that is wider than desired. Sugar microspheres also can be reactive with certain active drug products and some nutraceutical ingredients, thereby causing a decrease in the overall stability of the dosage form. When employed in coated applications, sugar microspheres can become tacky and hinder drug layering during the coating process. Because the sugar is water soluble and can dissolve when it comes in contact with aqueous coatings, the sugar cores can become difficult to coat and can stick to each other and to the surface of the pan. Also, certain applications, such as use of microspheres in pharmaceutical products, require cores that are less soluble than sugar-based cores to prevent agglomeration during processing and for effective stability and dissolution.
Microspheres based on microcrystalline cellulose (MCC) can provide an inert core for drug layering and coating. MCC-based microspheres are relatively dense and most have a relatively smooth surface to allow for uniform dosage of the active ingredient being applied to the core. However, the particle size distribution of MCC-based microspheres often is not uniform. Also, MCC microspheres are cost prohibitive for many economical finished dosage formulations and can absorb moisture from the coating process, which is undesirable in many embodiments because moisture absorption can cause decreased stability of the finished dosage form.
Starch microsphere cores also are known. Presently, these cores are not readily available commercially and are not available in the small particle size desired by many finished product manufacturers. Both sugar-based and MCC-based microspheres are believed to exhibit a change in solubility profile over time. Some studies have shown the dissolution of a coated sugar core may decrease over time, thus reducing the dosage of the active ingredient being released while the dissolution of a coated MCC-based core may increase over time, increasing the amount of active ingredient being released.